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Goldin Quits Top Space Agency Post, But His Legacy Lingers

Andrew Lawler

Revolution is an overused term in Washington, a city always claiming to be reinventing its institutions. But when NASA chief Dan Goldin departs next month after nearly a decade of service, he will leave behind a U.S. civilian space program that even his harshest critics say has been streamlined, modernized, and made more flexible. Unfortunately, Goldin is also walking away from an agency struggling with huge cost overruns on the space station, an aging shuttle system, and a simmering revolt by life and microgravity scientists. And his take-no-prisoners management style has created a power vacuum within the agency's upper ranks.

A 30-year veteran of the aerospace industry, Goldin imposed a “faster, cheaper, better” philosophy on an institution that had grown accustomed to multibillion-dollar science and human space flight efforts, each of which required decades to complete. “He was somewhat brilliant in technical matters and had the social skills and stamina to get across his message,” says one veteran agency manager. “For the most part, he succeeded in his revolution—and the science program is better for it.” But the cost of that revolution was high, say those who worked with him. “The change was difficult: He was a brutal person to work for,” recalls Wesley Huntress, who served as Goldin's space science chief and who now is a geophysicist at the Carnegie Institution of Washington.

Goldin's resignation came after the White House declined to send a signal that it wanted him to remain, even though it has been having trouble finding a successor, according to Administration sources. He went public with his decision on 17 October, 1 day after his chief of space flight, Joseph Rothenberg, announced his retirement. Goldin will leave in mid-November. Because the deputy administrator slot has never been filled under Goldin's tenure, the two vacancies will leave the agency very thin at the top. Former Senator Jake Garn (R-UT) and Thomas Moorman, an aerospace executive and retired Air Force general, are rumored to be current candidates for the top job.

Friend of science.

Dan Goldin nurtured space science at NASA, including a planned Europa mission that will search for life on the Jovian moon, even as funding for human space flight dropped significantly during his tenure.

CREDITS: (TOP TO BOTTOM) RICK KOZAK; SOURCE: NASA

Goldin was named administrator in April 1992 after a series of agency embarrassments, including the Hubble Space Telescope's faulty vision. He wasted no time in revamping mammoth projects. Under his tenure, for example, the $15 billion Earth Observing System was split up into large and small satellites, while a series of smaller planetary spacecraft were openly competed. The 1993 failure of the $1 billion Mars Observer gave Goldin the chance to apply that philosophy to the agency's Mars program. But the approach—which resulted in the successful landing of the innovative Mars Pathfinder—was called into question after the 1999 failures of the Mars Polar Lander and Mars Climate Orbiter, mishaps that many blamed on hasty attempts to cut corners on costs. Goldin also tried to cancel the $3 billion Cassini mission to Saturn in favor of less massive approaches, but he lost out to congressional and scientific pressure to spare the program.

Despite those defeats, Goldin is credited with a successful reformulation of NASA's scientific goals. “He raised the level of space science in the agency,” says Huntress. Adds John Logsdon, a political scientist at George Washington University, “He made the science program conceptually interesting, and now it has a strategic vision.”

Goldin's most ambitious attempt to rethink the agency's scientific mission built upon the discovery of purported evidence of ancient fossil life in a Mars meteorite found in Antarctica (Science, 16 August 1996, pp. 864 and 924). That announcement, although controversial, invigorated efforts at NASA to find extrasolar planets and explore bodies within the solar system, such as Jupiter's moon Europa, where conditions may be conducive to life. The approach, using the Hubble Space Telescope and future missions, won strong backing from the Clinton White House.

But other pieces of Goldin's science legacy shine less brightly. He was late in revamping the agency's troubled life and microgravity sciences program, which remains stymied by a lack of leadership, flight opportunities, and respect from the larger biological and physical sciences communities. The space station's voracious appetite for construction funds has put planned scientific facilities on the back burner. And recent moves to scale back crew size on the station may limit the number and scope of life and microgravity experiments that can be performed there.

Goldin's proclivity to use and discard managers could cause problems for his successor. “He left no disciples, no legacy within the ranks,” says one senior government official who worked closely with him. His abrasiveness and the fact that he was a holdover from the Clinton Administration left him without support in the new White House, placing him in limbo since January, aides say. But even without friends or a following in the Bush Administration, Goldin's revolution may now be so deeply rooted that it cannot be reversed.

NASA

Tight Budget Forces Agencywide Review

Andrew Lawler

The first task awaiting NASA's next administrator is likely to be damage control. The White House has asked agency managers and outside advisers to find ways to squeeze NASA's budget and hold down costs for the U.S. share of the international space station.

“This is a major reexamination of the agency,” says Charles Kennel, director of the Scripps Institution of Oceanography in La Jolla, California, and chair of NASA's Advisory Council. Senior agency officials are drawing up a list of proposed institutional changes, from mothballing the facility that handles Apollo lunar samples to giving universities responsibility for operating spacecraft, that the council will review in early December. In the meantime, an independent panel chaired by retired aerospace executive Thomas Young is expected to issue a report next week on how NASA should handle space station overruns without decimating plans for conducting scientific research on it. Sources say the program, which faced a $5 billion overrun last year, remains more than $1 billion in the hole despite significant trimming.

Both the institutional study and the space station report stem from the Bush Administration's desire to curb the growth of NASA's annual budget. Congress may finish work this week on a 2002 request for $14.5 billion—$200 million more than in 2001—that allows few initiatives. “It's impossible at this stage to do all the good things NASA wants to do,” says Rafael Bras, a hydrologist at the Massachusetts Institute of Technology and a member of the Advisory Council. “We are very, very concerned.”

BIOTERRORISM

Researchers Question Obsession With Cipro

Martin Enserink

Everybody loves Cipro. In the aftermath of deadly bioterrorist attacks on U.S. soil, the first line of defense against anthrax has reached Viagra-like status: Many people are suspected of hoarding it, or even gulping it, and supplies at pharmacies are running out. Some have urged the government to break Bayer's patent on ciprofloxacin, as the compound is officially known. As NBC news anchor Tom Brokaw—himself the target of one of the mail attacks—put it: “In Cipro we trust.”

But some scientists warn that the current obsession with Cipro is unwarranted and may backfire. Other, cheaper antibiotics can treat anthrax, they argue, and popping too much of the drug may create resistance in other pathogens. It might also tempt future bioterrorists to produce Cipro-resistant strains of Bacillus anthracis—which a recent study by U.S. scientists shows is possible.

So what exactly catapulted Cipro to drug manufacturer's heaven? The roots of Cipro's popularity go back to the Gulf War, says C. J. Peters, a former deputy commander of the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) in Fort Detrick, Maryland. When Operation Desert Shield was launched in 1990, the U.S. suspected Saddam Hussein of having a biological warfare program that included anthrax, and vaccines were in short supply. Peters—who is now director of the Center for Biodefense at the University of Texas Medical Branch in Galveston—says he and other experts had a “little huddle” to choose the best antibiotic out of dozens available to counter the threat. Their biggest concern, he says, was that Iraq would develop resistant strains. So the group focused on ciprofloxacin, which not only killed anthrax readily in the test tube but was also relatively new, minimizing the chance that Iraq had figured out how to elude it. A quick experiment by USAMRIID's anthrax expert Arthur Friedlander showed that the drug worked well in monkeys, says Peters. “So we said: Go with Cipro!”

As a result, Bayer supplied the government with 30 million tablets of Cipro during the war, according to a company slide show posted at the U.S. Food and Drug Administration's (FDA's) Web site. That marked the beginning of the drug's ascent. In 1998, it appeared as the drug of choice in the Army's Medical Management of Biological Casualties Handbook. In 1999, a group of experts published a so-called “consensus statement” about anthrax biowarfare in TheJournal of the American Medical Association. Their conclusion: As long as the anthrax strain is unknown, Cipro is the best bet, because there have been no published reports about resistance.

Drug of the day.

Overreliance on Cipro may tempt future terrorists to create resistant strains; a recent study shows that it can be done.

CREDIT: STEVEN E. FRISCHLING/CORBIS SYGMA

But the group, headed by Thomas Inglesby of the Johns Hopkins Center for Civilian Biodefense Studies in Baltimore, Maryland, also concluded that once researchers find out that the strain is vulnerable to other antibiotics, doctors should just go with “the most widely available, efficacious, and least toxic” one. Cipro can cause a series of side effects, which some believe may be especially serious in children.

In August 2000, the FDA added Cipro to the list of antibiotics approved for use in victims of anthrax inhalation. But it's not better than other antibiotics, says Peters; the edge that it had 10 years ago—its newness—is long gone. Besides, “if you rely too much on Cipro, you're inviting people to create resistant strains,” says Paul Keim of Northern Arizona University in Flagstaff.

In fact, Keim and his colleagues have already done just that, they reported at a recent meeting. Their goal was to find the mutations that make B. anthracis invulnerable to the drug, which could help quickly detect other Cipro-resistant strains in the future. To minimize the risk, the team used a weakened anthrax strain, but for microbiologists who know the literature, Keim says, producing a virulent Cipro-resistant anthrax might be feasible. Keim's team is not going to add to that literature, at least for now. “We have a paper ready to go,” says Keim, “but I think I'm going to sit on it.”

Meanwhile, two papers published online by Nature this week record progress in battling B. anthracis on another front. Although antibiotics readily kill the bacteria, patients with inhalation anthrax often succumb to bacterial toxins circulating in their blood (Science, 19 October, p. 490). In one study, researchers at Harvard University and the University of Wisconsin, Madison, report finding a receptor that the toxin uses to enter macrophages, the cells it kills. A soluble version of the receptor added to macrophages grown in a test tube could bind the toxin and prevent its entry into the cells—thus offering hope of a drug that could “mop up” the toxin.

In the second paper, researchers from six institutions in the United Kingdom and the United States announce having solved the three-dimensional structure of a component of the toxin called the lethal factor. The structure may give researchers new leads to block its main effect: killing patients in the advanced stage of anthrax.

COUNTERTERRORISM

U.S. Science Agencies Begin to Lend a Hand

The U.S. government last week took the first steps toward developing a coordinated scientific effort to combat terrorism. Despite an official blackout on the event, Science has learned that White House science adviser Jack Marburger called together the Bush Administration's top scientists on 19 October to discuss how their research programs can contribute to the antiterrorism campaign. At the same time, the National Academy of Sciences (NAS) has begun its own effort to shape government research plans in the wake of 11 September and the continuing anthrax attacks.

The White House meeting marked the first time that research managers from across the government gathered en masse to take stock and begin shaping a coordinated response. The federal mobilization has been hampered by the unofficial status of the government's top scientist: Marburger hadn't been confirmed by the full Senate at the time of the meeting, although lawmakers were expected to approve his appointment this week.

Many government science agencies did swing into action within hours of the assaults, but until now, there has been little coordination or long-term planning. The Department of Energy's (DOE's) national laboratories have loaned experts in biological and chemical weapons to intelligence and investigation agencies, for instance, and the National Science Foundation (NSF) has funded several shoebox-sixed experimental robots that searched for survivors and remains in the wreckage of the World Trade Center in New York City.

The lengthy White House meeting attracted more than a dozen federal officials who oversee the nation's $90 billion R&D portfolio, according to several participants. It focused primarily on briefing Marburger and his staff at the Office of Science and Technology Policy (OSTP) on the strengths and weaknesses of relevant research programs. OSTP would not comment on the meeting, citing Marburger's status as a consultant, but an aide to one participant said that officials “laid out what they thought they could offer and where they might need some help.”

Rapid response.

Scientists used NSF quick grants to develop a three-dimensional laser map of damage at the World Trade Center site and deploy robots to search the wreckage.

Some agencies have already spent weeks combing their portfolios for projects germane to the nation's defense. At the DOE's National Nuclear Security Administration, chief scientist Maureen McCarthy has asked the department's 17 national laboratories to “compile a list of their top five or 10 areas of expertise.” If the labs can't “respond to this war on terrorism, we probably shouldn't be in business,” she says, adding that the attacks have given the labs “a unifying sense of mission” unseen since the end of the Cold War.

At the National Institutes of Health, the National Institute of Allergy and Infectious Diseases is “accelerating” work on smallpox vaccines and drugs, says director Anthony Fauci (Science, 19 October, p. 498). It is launching studies to see if a five- or 10-fold dilution of the country's limited supply of smallpox vaccine would still raise a robust immune response. The institute has also ramped up efforts to test a new anthrax vaccine in clinical trials. “We have a meeting every morning on these issues,” says Fauci.

NSF officials are already seeing the preliminary results of some of nearly two dozen grants of $15,000 to $40,000 each the agency made soon after the 11 September attacks. Video of a University of South Florida robot probing the smoking Trade Center ruins, for instance, was featured at the 11 October meeting of the National Science Board, which oversees the agency. NSF-funded engineering studies of the Trade Center collapses, including steel analysis conducted by Abolhassan Astaneh-Asl and colleagues at the University of California, Berkeley, will be discussed at a mid-December workshop in New York City. And this week, Tom Smith and Ken Rasinski of the University of Chicago's National Opinion Research Center released the preliminary results of an agency-funded, nationwide psychological survey that compared how Americans responded to the 11 September attacks and the 1963 assassination of President John F. Kennedy. In general, the survey of 2100 people found that people were angrier, but less psychologically shaken, by the terrorist assaults than by the president's death.

Deciding where such studies might fit into a comprehensive antiterrorism research agenda will be the job of an NAS task force expected to issue its first findings by next March. NAS officials expect to recruit up to 20 panelists for the study, to be led by biologist Richard Klausner, former head of the National Cancer Institute, and Lewis Branscomb, a science policy expert at Harvard University. The effort is expected to become a major conduit for advice from the academic community to the White House on how scientists might contribute to the global battle against terror.

UNIVERSITIES

Family Moves to Give Institute to Harvard

Andrew Lawler

BOSTON—A small but prestigious institute on the banks of the Charles River, the legacy of Polaroid founder Edwin Land, may soon become part of Harvard University. The Land family has offered the Rowland Institute for Science in Cambridge, Massachusetts, to the university as a gift, according to several sources familiar with the negotiations. If the deal pans out, the institute—and its endowment—will be incorporated into Harvard's arts and sciences program. The offer is a coup for the university, given its severe shortage of space and the prime location of the institute just a few kilometers from the main campus. But the change could spell the demise of the institute's novel line of basic research.

Land, inventor of instant photography, set up the institute in 1980 to conduct a wide range of basic research in physics, chemistry, and biology. Rowland has an annual budget of $7.5 million, more than two dozen researchers, and an endowment between $50 million and $100 million, according to Michael Burns, the institute's research director. Housed in a 10,000-square-meter building, the institute employs about 70 people. Sources close to the talks say that members of the Land family—who declined to discuss the issue—have decided the institute is too expensive to maintain.

Harvard bound?

Researchers worry that the unique Rowland Institute will lose its identity if it is transferred to Harvard.

CREDIT: ROWLAND INSTITUTE FOR SCIENCE

The proposed merger is “an imaginative concept from the Rowland, which has an impressive history of fostering new cross-disciplinary research,” says Jeremy Knowles, dean of Harvard's faculty of arts and sciences. Knowles adds that the merger could strengthen the Rowland Institute while providing “new opportunities for scientific research and teaching at Harvard.” But the fate of Rowland's researchers and their work is unclear. “We have absolutely no idea what's going on,” says institute microbiologist Diane Schaak. “We're not very happy, and we worry about the big machinery of Harvard taking over.”

A team of Harvard researchers recently reviewed the institute. The Rowland scientists “are eclectic and interested in high-risk and high-return research,” says Harvard biologist Markus Meister, who participated. The team recently submitted a paper to Knowles on the institute's future should Harvard assume control. One suggestion was to convert it to the neuroscience center now in the planning stage (Science, 24 August, p. 1419). Meister, who declined to discuss the report in detail, concedes that the Charles River facility “is not the ideal location,” as the goal of the neuroscience center is to encourage interdisciplinary work among Harvard departments.

The Land family is reportedly eager to complete the deal soon, and Knowles says that both sides will work on the details in the coming weeks. As for the Rowland researchers, “we all have our CVs ready,” says Schaak.

NEUTRON SOURCES

Compromise Lifts Hopes for German Reactor

Gretchen Vogel

BERLIN—A reactor designed to produce neutrons for research cleared a political logjam this week and moved one step closer to beginning operations. Feuding politicians said they had reached a compromise that could allow researchers to power up the FRM-II facility in Garching, outside Munich, although it will likely be several months before studies can begin. The compromise is welcome news to scientists who had worried that the reactor might lie dormant until after Germany's national elections in September 2002.

Construction of the $500 million FRM-II neutron source was completed on schedule this summer. But the federal government in Berlin, led by a coalition of Social Democrats and the Green Party—a vocal opponent of nuclear energy—has delayed giving the reactor final permission to start. The reason: The reactor will use highly enriched uranium fuel, a potential ingredient in nuclear weapons. The federal government announced in March that it wanted the reactor to switch to medium-enriched uranium by 2006 (Science, 30 March, p. 2527), but FRM-II researchers and the Bavarian state ministry of science said such a rapid switch was technically infeasible, leading to a deadlock.

Now the two sides have reached a compromise. On 17 October, Wolf-Michael Catenhusen, the federal government's parliamentary secretary for research and education, and Bavaria's science minister, Hans Zehetmair, agreed that the reactor would switch to medium-enriched uranium after 10 years. The 10-year timetable is realistic, says physicist Winfried Petry of Technical University in Munich, and the agreement signals that “there is a political will to take the thing into operation.”

Ready to go.

The long-delayed FRM-II reactor may finally get the green light.

CREDIT: FRM-II

The reactor still faces one more hurdle, however: The environment minister, Jürgen Trittin, a member of the Green Party, must give his approval. Trittin told Science this week that he will do so as soon as FRM-II officials present an acceptable plan for dealing with the reactor's radioactive waste. That requirement is standard for new reactors, but it could lead to more delays if the facility becomes caught in ongoing national controversies over nuclear waste storage in Germany. Trittin is also waiting for a final recommendation on FRM-II from the national radiation protection commission, which is not scheduled to meet until December. Zehetmair says he is optimistic that the environment ministry will not delay further. “Based on our recent talks, we expect the ministry to give permission early next year,” he told Science.

Project leaders have warned that if the standoff lasts much longer, they fear a mass exodus of talented researchers. Already at least 15 of 100 researchers involved in the project have left, in part because of the uncertainty, Petry says: “It is more than disappointing to do nothing but sit and wait for a commission that will not even meet until December. All the instrumentation is ready, and we are waiting.”

JAPAN

Summit Seeks Boost for Life Sciences

Dennis Normile

TOKYO—A powerful group of biotechnology industry leaders gave the Japanese government a wish list this week: better coordination of government spending in the life sciences and increased emphasis on commercializing the results.

The proposals, drawn up by the Japan Association of Bioindustries Executives (JABEX), represent an unusual effort by industry to affect academic research. They were released at a Life Science Summit here involving some 600 industry, academic, and political leaders. The proposals are expected to get a sympathetic hearing, thanks to the group's political connections and the administration's policy of emphasizing research with a potential economic payoff.

Katsuhiro Utada, chair of the major food processor Ajinomoto Ltd. and also head of JABEX, says that life science research in Japan is not generating the same social and economic returns as in the United States and Europe. The group argues that current efforts are hamstrung by the diffusion of government support for the field, which is divided among five ministries and several public corporations. More importantly, Utada says, “there is no strategy for the smooth and speedy commercialization and industrialization of basic life science research results.”

Looking for direction.

Katsuhiro Utada heads a Japanese industry group that wants better coordination in the life sciences.

CREDIT: D. NORMILE

JABEX wants the government to establish a task force, chaired by the prime minister, to develop and oversee a comprehensive strategy for everything from basic research to industrial biotechnology processes. It also urges the creation of a committee to review existing programs, with funding linked to the evaluations and the panel's priorities.

Researchers are intrigued by some aspects of the proposals. Michio Oishi, a molecular biologist who heads the Kazusa DNA Research Institute in Chiba, says that applying the same review criteria to all life science projects could benefit university researchers. They now compete for smaller awards and typically have their work scrutinized more closely than do their colleagues at national research institutes. “I think professors at universities would welcome this move,” he says.

Less welcome would be any move to reduce the number of funding sources—a move the industry group has not advocated, although media reports have incorrectly described the plan as a proposal to create a Japanese National Institutes of Health. Some scientists also worry that the task force could overlap with the work of the new, top-level Council for Science and Technology Policy.

The fate of the proposals is uncertain, but industry leaders are heartened by a message to the summit from Prime Minister Junichiro Koizumi, who said it is “very important to develop a strategy for life science research.” Koji Omi, the minister for science and technology policy, promised to “take all these opinions into consideration” in plotting the future of life science research in Japan.

CHINA

First Western Chair Named at Qinghua

BEIJING—When Purdue University's Gavriel Salvendy met with a delegation from China's prestigious Qinghua University last spring, he had no idea they were on a recruiting mission. But this month Qinghua made history by appointing Salvendy as chair of its new industrial engineering program. Salvendy, who will divide his time between Qinghua in Beijing and Purdue in West Lafayette, Indiana, will be the first foreign scientist to head a university department in China since the Communists came to power in 1949.

Salvendy's appointment is part of a larger effort by Qinghua, already regarded as China's top technology school, to recruit outsiders to further raise the quality of its academic programs. “I'm the guinea pig,” says the 63-year-old Salvendy, who was born in Czechoslovakia, raised in Israel, and trained in Europe before coming to Purdue in 1971. Qinghua officials say they plan to offer key positions to some 50 leading Western scholars in the next 5 years, financed by contributions from wealthy Chinese companies within the country and overseas. “We wish to build up our industrial engineering department to international standards in education and research as soon as possible,” says Lin Heng, vice chair of the new department. “With Professor Salvendy as our dean, we are hopeful of achieving our goal.”

Honored.

Gavriel Salvendy gets a pioneering post at Qinghua University.

CREDIT: COURTESY G. SALVENDY

Salvendy's first nine faculty appointments are all native Chinese—“I didn't have the option of hiring from the outside,” he says. But greater interaction with the United States is a priority. “Each year we will have three U.S. professors teaching and working in China for 1 month, and there will also be a student exchange program between the two universities. The idea is to move totally to English instruction within 3 years.”

Salvendy, an expert in human-machine interactions and a member of the U.S. National Academy of Engineering, adds his Qinghua duties to an already full plate as the NEC professor of industrial engineering at Purdue and founding editor of three international journals. He says that he wouldn't have taken the job at any other school: “I've had 10 Ph.D. students from Qinghua in the last decade, and the quality of their work is phenomenal.” He expects to spend 1 month a year in Beijing, and his $100,000-a-year salary—more than 10 times what the average Chinese academic earns—will go into a special fund to support his Purdue lab.

Being an outsider may even work to his advantage, Salvendy says. “You know,” he jests, “that companies always listen more closely to consultants than to their own people.”

CLIMATE CHANGE

A Little Sharper View of Global Warming

Richard A. Kerr

With scientists suggesting that the globe could warm by at least a couple of degrees by the end of the century, members of Congress want to know exactly what's going to happen in their city-size districts back home. Who will the winners and losers be, they ask? Tough as the question is to answer at the local level, researchers are starting to see a glimmer of improvement in predictions of regional climate change: an emerging consistency in model calculations of temperature and precipitation for subcontinental-scale regions. “To me, it's quite surprising that the response [of the models] is so consistent at the regional level,” says modeler Filippo Giorgi of the Abdus Salam International Centre for Theoretical Physics in Trieste, Italy. “Now the models are starting to show some patterns,” ones that suggest a distinctly uneven impact of greenhouse warming.

A mixed bag.

Climate models call for greater-than-average greenhouse warming (orange) over most of North America and less-than-average warming (yellow) some seasons in South America, but often they can't agree (pink).

SOURCE: F. GIORGI/ABDUS SALAM ICTP

The hints of coming regional changes are in the just-published U.N.-sponsored report Climate Change 2001: The Scientific Basis (Cambridge University Press), for which Giorgi and Bruce Hewitson of the University of Cape Town, South Africa, were coordinating lead authors of the regional climate chapter. The chapter examined forecasts by nine state-of-the-art global climate models, the largest number ever compared at a regional scale. With a sharper view of climate and improved representations of key atmospheric processes, this latest generation of models is “definitely doing better” at reproducing current climate on a regional scale, says Giorgi.

The new comparison confirms the previously reported much-greater-than-average warming in winter at high latitudes, as well as the greater-than-average increase in precipitation there. But it also pushes a greater-than-average warming down into northern midlatitudes. The June-July-August period would warm less than average over southern South America, South Asia, and Southeast Asia. In much of the tropics and subtropics, however, most models disagreed widely about how far temperatures would rise. Predictions for precipitation were less consistent, except at high latitudes, although the consensus called for a stronger summer monsoon across most of Asia and drier winters in Australia and southern Africa.

Climate researchers welcome the regional-scale comparisons. “I think this is heading toward more quantifiable estimates of reliability,” says modeler Gerald Meehl of the National Center for Atmospheric Research (NCAR) in Boulder, Colorado. But “we've got a ways to go in producing good regional projections,” warns meteorologist Kevin Trenberth of NCAR. “Simply because models agree doesn't mean they're right.” They could agree in a region because they are all wrong in the same way, he notes, such as not reproducing the effects of El Niño. To be sure that models are agreeing for the right reasons, more and ostensibly better models must be compared.

Collateral Damage

With reporting by Pallava Bagla in New Delhi, Vivien Marx in Boston, and Aude Sonneville in Cambridge, U.K.

The war in Afghanistan and rising tensions in the Middle East have temporarily put on hold efforts by scientists from Islamic nations to strengthen ties among themselves and with the West

Farouk El-Baz led the team that chose where the Apollo landers set down on the moon. So mapping groundwater on the Arabian Peninsula figured to be a cinch for the Egyptian-born director of Boston University's Center for Remote Sensing. But that was before the 11 September terrorist attacks on the United States. The planned trip to Sharjah in the United Arab Emirates (UAE) for fieldwork has been put off indefinitely, he says, because “people just didn't feel right” about traveling there now.

The suspension of such collaborative projects, of course, cannot be compared on any scale to the tragedy of the attacks and the current war in Afghanistan. But they pose a significant interruption to what in the last few years has been a loosening of the ideological shackles on Islamic science. Increasing ties with Western colleagues over the past decade have allowed researchers in many Islamic countries to convince their leaders of the value of science. In the Islamic world, “the tragedy has been a lack of comprehension of how important scientific research is to development,” says Abdulkarim Al-Eryani, a Yale University-trained microbiologist who now serves as political adviser to Yemen President Ali Abdullah Saleh.

One vehicle currently being pursued for stimulating science in the region is a nascent agency, based in the UAE, that would be modeled on the U.S. National Science Foundation (NSF). Some opinionmakers are also arguing for a Marshall Plan to restore the Islamic world in the same way the huge U.S.-led investment helped rebuild Europe after World War II. “The gap is far too wide between the haves and the have-nots, and science would be a wonderful vehicle to help bridge that gap,” says Egyptian-born chemist Ahmed Zewail, director of the Laboratory for Molecular Sciences at the California Institute of Technology in Pasadena and the first Arab (and second Muslim after Abdus Salam of Pakistan) to win a Nobel Prize in science.

But progress on such ideas has been halted by the tensions stemming from the war in Afghanistan and the continuing Palestinian intifada. And there is risk of a permanent setback. “Damage to long-term relations and scientific collaboration can be limited only if the Afghan war is short and targeted against the criminals,” says chemist Atta-Ur-Rahman, Pakistan's minister for science and technology.

Voices in the wilderness

A thousand years ago, Muslim scientists were pioneers in astronomy, theoretical physics, and mathematics, and they invented algebra. “The Islamic world was a cradle of scientific innovation, creativity, and advancement at the beginning of the last millennium,” noted Iran's president, Mohammad Khatami, at a meeting of the Third World Academy of Sciences in Tehran last autumn. Islam, he said, values thinkers and scientists because acquiring knowledge “prepares the believer to practice his duties with perfection.”

Over the centuries, however, that message was diluted as Islam's spiritual leaders began to reject European ideas and innovations. “We inherited a Dark Age of refusing new thinking and theories,” says Al-Eryani, who adds that in some Islamic countries, “science has become a slave of religion.” Perhaps the most obvious clash is over the theory of evolution, which isn't even mentioned in textbooks in some Islamic countries. Darwinism “has essentially been banned” in Yemen and many other nations, says Al-Eryani, although in his view “there is no contradiction between Darwinism and religious faith.”

Despite the skepticism of clerics and the growth of Islamic fundamentalism, the past decade has seen shoots of scientific growth in many Islamic countries. The most recent available statistics for the Arab world, from the United Nations Educational, Scientific and Cultural Organization's (UNESCO's) World Science Report 1998, put R&D spending at $780 million in 1996—a mere 0.14% of the region's gross domestic product, but a 43% rise over 1992 levels. Four countries—Egypt, Kuwait, Morocco, and Saudi Arabia—accounted for 72% of this R&D spending, but the growth has been widespread. In addition, Iran, not classified as an Arab nation in the report, last year spent about $350 million on research and higher education (Science, 24 November 2000, p. 1484).

Laying a foundation.

Farouk El-Baz helped the Sultan of Sharjah launch one scientific tool essential to the Arab world: a foundation that will hand out peer-reviewed grants.

CREDIT: LYNNE FIELDING/BOSTON UNIVERSITY

Helping fuel enthusiasm for science was Zewail's Nobel in 1999, a solo award for his pioneering use of ultrafast spectroscopy to study chemical reactions. “There was great rejoicing throughout the Arab world,” recalls Zewail, who used his influence to persuade Egypt's leaders to start building a new science and technology university near Cairo. However, the country's economic woes and the Middle East turmoil have slowed the project since a groundbreaking ceremony early last year.

One place where the scientific awakening is especially evident is Yemen (see sidebar). Emerging in the 1960s from self-imposed isolation, the oil-poor nation has pushed hard to foster scientific cooperation in the region. Yemen's government has organized a major meeting in each of the past 4 years, including one earlier this month, aimed at brokering regional ties in all fields of science. Nurturing this scientific enlightenment are key individuals such as Al-Eryani and Moustafa Bahran, a neutrino physicist trained at the University of Oklahoma who is science adviser to Yemen's president. “We want science to be integral to the fabric of the country,” says Bahran. “Nobody in his right mind would say that scientific research is not important to development.”

But the fighting in Afghanistan and the unsettled political situation have cast a pall over the region that has darkened the immediate outlook for science. Dozens of conferences have been shelved, including the Third World Academy of Sciences annual meeting scheduled for next week in New Delhi. From Casablanca to Karachi, field expeditions and lab-to-lab exchanges are coming under scrutiny, with many being cancelled or postponed indefinitely.

“I do not feel at liberty to travel to any country in the Middle East right now,” confesses Harald Kehl of the Technical University of Berlin, who leads a mountain ecosystem project in southeastern Turkey. He worries that local people “may see me and my fieldwork as part of a hostile maneuver of some sort.” Population geneticist Gordon Luikart of Joseph Fourier University in Grenoble, France, who studies the genetics of wild sheep, has postponed an upcoming excursion to eastern Turkey: “I would not want to have to show my American passport [there].”

In better times.

Laurent Marivaux, examining a piece of sediment with tooth remains, hopes to return to Balochistan with his French colleagues in the spring.

CREDIT: STEPHANE COMPOINT

Reflecting the jitters of research officials, a manager at France's basic research agency, CNRS, issued a strongly worded communiqué on 12 September urging scientists to forgo travel to Arab countries. Although the CNRS—under pressure from the Ministry of Foreign Affairs—retracted the memo 2 days later, the original notice has clearly had a chilling effect on travel to the region. One group exercising prudence is Laurent Marivaux and his colleagues at Université Montpellier II, who have postponed fieldwork in Balochistan, a province in Pakistan where they and local scientists have unearthed stunning lemur fossils dating back 30 million years (Science, 19 October, p. 587). Team member Jean-Loup Welcomme says his group intends to return in the spring: “I'm sure we'll always be welcome there.”

Some regional efforts have hit snags as well. For example, the U.S. National Cancer Institute has put off a visit this month by U.S. scientists to Egypt, Jordan, Israel, the Palestinian Authority, and Cyprus to inspect cancer registries under the Middle East Cancer Consortium. And a U.S. National Institutes of Health project on hypertension in the region, officials say, is now dormant.

A promising future?

Once the crisis is over, Western scientists hope to strengthen their nascent links to the Islamic world. “There is a feeling that a resolution of the current situation may actually make work easier in places like Tajikistan, Uzbekistan, Turkmenistan, and perhaps even Iran,” says Steve Roecker, a geophysicist at Rensselaer Polytechnic Institute in Troy, New York. Roecker, who does seismic fieldwork in Central Asia, even foresees the possibility of returning someday to the Hindu Kush in Afghanistan, where he did his thesis research in the mid-1970s.

One major regional collaboration still on track is SESAME, an international research center being built at Al-Balqa' Applied University near Amman, Jordan. The SESAME project began in 1999 when Germany offered to give the Middle East BESSY-I, a 0.8-giga-electron volt synchrotron in Berlin that had been replaced by a newer model. “The problems with terrorists have so far had no influence on SESAME,” says Herwig Schopper, a former director-general of CERN, the European particle physics lab near Geneva. Schopper has worked tirelessly to spearhead the project in collaboration with UNESCO. The 11-nation consortium that's building the center is now on track to receive shipment of BESSY's components in early 2002.

The region is hoping to import grantmaking as well as Western hardware. A promising initiative is the Arab Science and Technology Foundation in Sharjah, UAE. The foundation began a few years ago when Sultan bin Mohammed Al-Qasimi of Sharjah—who holds a Ph.D. in agricultural science—invited experts, including El-Baz of Boston University, to brainstorm ideas for improving science in the Islamic world. El-Baz and his colleagues concurred that what the region needed most was a grantmaking body for science: a “mini-NSF,” El-Baz says. The sultan started the endowment with $1 million of his own fortune. El-Baz and others have just embarked on a fund-raising drive to increase the pot to $100 million.

Thinking ahead.

The first science Nobelist born in an Arab country, Caltech chemist Ahmed Zewail is one of many prominent figures calling for a “Marshall Plan” to build research capacity in Islamic countries once the crisis abates.

CREDIT: CALIFORNIA INSTITUTE OF TECHNOLOGY

Even that amount could seem like peanuts, however, if a scientific Marshall Plan for the Islamic world were to take shape. Scientists and politicians have begun preliminary talks about holding an Arab summit on scientific development next year. They're making a wish list for some of the richer nations in the region. Pakistan's Minister Atta told Science that he would like to see the 57 countries of the Organization of the Islamic Conference contribute $10 billion over 3 years to such a fund. What is needed, he says, is “a head of an Islamic state, like the King of Saudi Arabia, who could champion the cause.” And there's an expectation that once the war ends, Europe and the United States may help rebuild the shattered economies of Islamic nations. “After the tragedy of September 11,” says Zewail, “I hope that the U.S. will take a new look and take a more active role in helping the region.”

The first fruits of the conflict, ironically, may be a reverse brain drain. Many Muslim scientists living in Western countries say they have begun feeling uncomfortable since the terrorist attacks. Pakistan is seizing the opportunity and trying to lure talent back home. Just in the past few weeks, Atta says, Pakistan's science ministry has offered positions to 23 expatriate researchers at three times the current salary of a full professor in Pakistan. So far, he says, 17 have accepted. Pakistani researchers will also benefit from the recent lifting of some U.S. sanctions.

But hope is tempered with a realism based on experience. “Anytime scientists in the Arab world want to collaborate, politics gets in the way,” says El-Baz. And no one knows when the region's politics will cool down enough to allow Islamic scientific initiatives to regain some of their lost momentum.

WAR ON TERRORISM

War Is Latest Assault on Progress in Yemeni Science

Richard Stone

MARIB, YEMEN—The chance to prove the existence of the Old Testament's most famous temptress, the Queen of Sheba, would normally be enough to attract many an archaeologist or adventurer to this southern fringe of the Arabian desert. But now, at what should be the height of the autumn excavation season, there is not an archaeologist to be seen in the sprawling Mahram Bilqis temple in what was the powerful Kingdom of Saba, from which traders once carried frankincense and myrrh across the Middle East and North Africa. On a sun-drenched October day, the only sign of life is a lone Bedouin guard in a billowing white frock and gray wool vest, with a traditional Yemeni curved dagger in a sash around his waist and a Kalashnikov assault rifle slung over his shoulder. Life-sized alabaster faces peer solemnly from a silent mausoleum half buried in drifting sand.

In the aftermath of the 11 September terrorist attacks, many field projects involving Western researchers have been put on hold. The interruptions extend even to a moderate Arab nation like Yemen that has aligned itself with the U.S.-led coalition and has so far seen only muted public protest against the bombing campaign in Afghanistan. That is why researchers from the United States and other countries who were supposed to have come to Marib this month remain thousands of kilometers away. “It was difficult in my heart but not in my mind” to postpone this season's dig, says Merilyn Phillips Hodgson, president of the American Foundation for the Study of Man in Falls Church, Virginia, the U.S.-led team's major backer.

Even under the best of circumstances, doing science in this part of Yemen can be difficult. Over the past few years, members of the Marib team had grown accustomed to traveling from their hotel to the site every day accompanied by armed guards to ward off potential kidnappers from a tribe hostile to the Yemeni government. They haven't been alone in needing protection. On his most recent foray to collect a moth unique to Yemen, University of Bonn entomologist Clas Naumann was assigned 10 heavily armed guards. “And they expect you to feed them, too,” he says.

Deserted.

Flanked by interior ministry guards, Yemeni antiquities official Sadiq Sa'id Othman inspects the dormant archaeological dig at the Mahram Bilqis temple, which Yemen hopes to see restored to the splendor of nearby Arsh Bilqis.

CREDITS: R. STONE

But the war in Afghanistan has sent the country's economy reeling, along with Yemeni science. Tourism, a major industry that typically crests in October and November, is down 90% from last year. And Yemeni scientists, like many of their counterparts throughout the Islamic world (see main text), are feeling increasingly isolated as Western colleagues shun travel to the region. A conference intended to forge collaborations in the applied sciences, held in the capital, Sana'a, earlier this month, had been expected to draw more than 200 researchers from Islamic nations outside Yemen and a few dozen from Europe and the United States. The actual attendance from abroad: 80 foreigners, including only Naumann from the West.

The disappointing turnout was another blow to the Yemeni scientific community, which had already endured a self-destructive decision by the government to side with Iraq during the Gulf War. Scientists have also had to be on guard against the sudden appearance of dozens of “scientific institutes” that introduce high-school-age children to religious fanaticism, says Abdul Wahed Mukred, vice chair of the Agricultural Research and Extension Authority in Dhamar, adding that the government has successfully converted most of the institutes into secular schools. In particular, two events have forced the government to crack down hard on fundamentalism. In December 1998, four tourists were killed when government forces stormed their kidnappers' hideout. Then last year, terrorists linked to Osama bin Laden blew a hole in the side of the U.S. warship Cole docked in the port of Aden, killing 17.

Despite the risks, the country still attracts Western scientists eager to make their mark. “The last time anyone studied spiders here was [in] 1890,” says Tony van Harten, a Dutch spider specialist in Sana'a who advises the Ministry of Agriculture and Irrigation on biological pest control. Collecting on behalf of dozens of specialists around the world, van Harten has helped discover nearly 130 novel species in Yemen. But he and others acknowledge that the long-term prospects for their work are clouded. “I have not yet bowed to the strong pressure to leave and abandon my work midstream,” says University of Chicago archaeologist Krista Lewis, who studies ancient food practices in the Yemeni highlands. But it's “nerve-racking,” she says, “to watch and wait and hope that things will not get worse than they are at present.”

Over the next several months, many other scientists will be watching and waiting before deciding whether it's safe to work in Yemen. “Any decrease in foreign cooperation is really going to hurt science in our region,” warns physicist Moustafa Bahran, who organized the Sana'a conference. Fewer outside collaborators, he says, would leave a fledgling scientific community even more adrift.

BIODIVERSITY

Up for the Count?

Andrew Lawler

An odd combination of high-tech gurus and senior taxonomists is planning an ambitious—some say quixotic—effort to catalog and describe all species on Earth

BOSTON—Making big lists is big science today. Backed by the latest in high-tech tools and millions of dollars in public and private funding, molecular biologists are busily pinpointing tens of thousands of genes, while astronomers are mapping millions of galaxies. So pity the taxonomists, who have yet to organize something equivalent for their field: a comprehensive, well-funded, highly coordinated effort to count and describe Earth's species.

But that will change if a small group of San Francisco high-tech movers and shakers has its way. Allied with senior researchers in the field, including Harvard professor emeritus E. O. Wilson and Peter Raven of the Missouri Botanical Garden, they are brainstorming an ambitious listmaking effort that could surpass the Human Genome Project or the Sloan Digital Sky Survey in complexity.

Their goal is to count every last animal, plant, and microbe on Earth, including the undiscovered ones that account for perhaps eight in 10 living species. Creating this biological master database, they estimate, would take at least 20 years, cost some $20 billion, and require the help of thousands of researchers and amateur naturalists around the world. “The idea is simple: a Web page for every species,” says Kevin Kelly, who started Wired magazine and who chairs the new All Species Foundation dedicated to the task.

The foundation assembled two dozen scientists last week at Harvard to help figure out how to tackle such a mammoth endeavor. As was clear at the meeting, the bold proposal is raising both the hopes and hackles of taxonomists. “This is well intentioned but incredibly naïve,” says Cristián Samper, deputy director of the Smithsonian Tropical Research Institute in Panama. Not only is the proposal impossibly ambitious, said many, but unlike counting genes or galaxies, counting species involves complex political, educational, and legal issues—ranging from the shortage of trained researchers in developing countries to concerns about biopiracy. And gaining public and private support for a $20 billion project—particularly during an economic downturn—strikes some as quixotic.

But the assembled scientists were also excited by the prospect of new funding, advanced computer tools to handle huge amounts of data, and an aggressive attempt to interest the public and politicians. And they clearly welcome any assistance Silicon Valley has to offer. “Systematic classification of biodiversity is at the beginning of a technology-driven revolution that will take it into the mainstream of science,” Wilson told the participants. “If we build it, they will come.”

The all-species-count concept sprouted not from a meeting of taxonomists but from a San Francisco dinner party in the spring of 2000. Former Microsoft chief technology officer Nathan Myhrvold invited friends such as Kelly of the All Species Foundation and Stewart Brand, who created the Whole Earth Catalog and now directs the Global Business Network, to discuss which philanthropic ideas might be worthy of large donations. Kelly tossed out the biological inventory idea, “but I assumed it was already being done,” he says.

On the ascent.

Isabella Kirkland's painting combines a host of invader species, such as the ring-billed gull, crowding out biodiversity.

CREDIT: ISABELLA KIRKLAND

Bits and pieces are. Ecologist Daniel Janzen of the University of Pennsylvania in Philadelphia made a start 7 years ago in a project—the All Taxa Biological Inventory—to catalog every life-form in one part of Costa Rica, but the effort fell apart amid disputes over funding and other issues. Now an international project called Species 2000 is working to inventory the 1.75 million known species by drawing on existing databases. So far, with funds from public and private sources, the project has completed 250,000 and hopes to reach 500,000 by 2003. In Copenhagen, the Global Biodiversity Information Facility, a new international organization, is gearing up to add new biodiversity data online.

But nobody had proposed a single effort to count all the world's species by a particular deadline, Kelly and Brand learned when they consulted the experts. They were also astonished to learn of the low-tech nature of the field. “Taxonomy is still done the same way it was during Darwin's day,” an incredulous Kelly told Science.

Kelly and Brand have set out to change that—by making taxonomy “cool,” Kelly says. With support from members of the California Academy of Sciences, they launched the foundation last year. Brand and his wife, foundation business consultant Ryan Phelan, kicked in about $40,000 and Kelly about $20,000. They have since won a $1 million grant from a wealthy entomologist. They also recruited Brian Boom, former vice president of botanical science at New York's Botanical Garden, to be the foundation's chief executive officer. “The refrain is think big, start small, act now—and don't deliberate it to death,” says Boom. They've picked a target of 25 years to complete the effort.

At the Harvard meeting, taxonomists suggested they start by taking on some manageable but still ambitious projects. For instance, the foundation could support four or five intensive surveys in particular countries; alternatively, it could take a novel approach and focus on a single species, such as the wood rat or the salmon. The idea is to catalog all the species that live in, on, or around the chosen animal. Along with yielding valuable scientific data, that approach could capture the public's imagination, said Kelly and Boom, who are counting on outside help.

“Let the rest of the world become naturalists, with the Web as the unifying glue,” says John Pickering, an ecologist at the University of Georgia in Athens. Amateurs could build “life lists” of new species seen or discovered, much as bird watchers do today, forming a critical base for research.

Whole-species catalog.

High-tech gurus Kevin Kelly and Stewart Brand are behind the push for a total species count in 25 years.

CREDITS: (TOP) MICHAEL SEXTON; (BOTTOM) TOM GRAVES

Counting all species would indeed require legions of taxonomists and parataxonomists as well as massive but user-friendly computer databases. And those legions would have to be concentrated in the most biodiverse parts of the world—the developing countries—where both trained naturalists and computer access are scarce. The foundation hosted a meeting in Mexico City earlier this fall to underscore its desire to involve developing-country scientists. But good intentions have failed before—such as in Costa Rica. And developing nations are concerned that Western countries might take advantage of their biodiversity for profit's sake (Science, 9 May 1997, p. 893).

And then, of course, there's the money. Whether the odd combination of high-tech gurus and academic taxonomists can ratchet a modest foundation into a multibillion-dollar international effort remains to be seen. Kelly hopes to raise $10 million by the end of 2002, mainly in large chunks from foundations and wealthy individuals. Phelan adds that the goal is to raise $50 million to $100 million in the next 3 years. “If we can deploy $3 million next year, we could kick-start things and get some traction,” she says.

Ultimately, the scale of the effort will require national and international funding. In the United States, at least, that may be hard to find: Biologists are still smarting from congressional rejection of the proposed National Biological Survey. Lawmakers feared a species inventory could ultimately infringe on the rights of owners of private property. But Raven, who moderated a session at the Harvard meeting, says that Kelly's foundation is an encouraging step. “The All [Species Foundation] effort is a publicity gold mine, if played right,” he says.

Many of the taxonomists at the Harvard meeting scoffed at the idea that an all-species count could be done in 25 years. But whether or not the California high-techies can pull it off, senior researchers welcome the nascent foundation and its infusion of funds. “People are spread out, underappreciated, and consider themselves fly or beetle or butterfly people rather than taxonomists,” says Scott Miller, entomology department chair of the Smithsonian's National Museum of Natural History. The big-list idea and help from Silicon Valley might prove just the tonic needed to give purpose, direction, and unity to a tradition-bound field.

INFECTIOUS DISEASES

Uncertainties Plague Projections of vCJD Toll

Michael Balter

Two mathematical models of the epidemic come up with very different results. Researchers may soon know if one is right

Since 1996, when a new human disease linked to eating beef from cattle infected with bovine spongiform encephalopathy (BSE)—“mad cow disease”—first emerged, the British public has been gripped by one question: How bad will the epidemic be? By late September 2001, 107 people living in the United Kingdom had died from variant Creutzfeldt-Jakob disease (vCJD), an invariably fatal neurodegenerative malady. But just how many more it might claim remains unclear.

Although an estimated 750,000 BSE-infected cattle were eaten by humans between about 1980 and 1996, no one knows how many people actually became infected, nor how long it takes for an infected person to become sick. Past projections of the possible death toll have not relieved the uncertainty. The most authoritative estimate to date predicts that cases could range from a few hundred to more than 100,000. The waters became even murkier last week when a study concluding that sheep might also have been infected with BSE—a possibility health officials have long feared—was pulled from publication at the last minute when it turned out that the scientists might have been analyzing brains of cattle rather than sheep (see sidebarsidebar).

In the midst of this confusion, two well-respected teams have been refining their projections—and they are coming up with different conclusions. A new mathematical analysis of the epidemic by researchers at the London School of Hygiene and Tropical Medicine provides some encouraging news. The study, published online by Science on 25 October (http://www.sciencexpress.org/), concludes that the epidemic might be nearing its peak and that the maximum number of cases might number no more than “several thousand.” The team, led by epidemiologist Peter Smith, believes that the real numbers could turn out to be much lower than that. Moreover, says veterinary epidemiologist Mark Woolhouse of the University of Edinburgh in Scotland, the new study's more optimistic predictions might be “very testable in the short term.” But these hopes are challenged by epidemiologist Roy Anderson's group at Imperial College in London. This group's newly completed but still unpublished analysis, which uses different mathematical techniques, comes up with maximum estimates that are “substantially higher,” says team member Neil Ferguson.

The fact that different mathematical models produce different results is not surprising, researchers say. Because reliable tests for BSE infection in humans do not yet exist, it is impossible to know how many people were actually infected and when. Without such data, modelers must rely on “arbitrary mathematical assumptions to guide the extrapolations,” says epidemiologist Peter Bacchetti of the University of California, San Francisco.

Until now, the most oft-cited projections were those reported by Anderson's team in the 10 August 2000 issue of Nature. Anderson and his colleagues explored more than 5 million combinations of parameters based on a wide range of assumptions, including the likelihood that an infection would result from eating BSE-laden cattle and the effectiveness of government attempts to control the spread of BSE. They came up with a maximum of 136,000 cases over the next several decades.

Good news?

If one mathematical projection is correct, the number of human cases may soon peak.

The London School team used a very different approach, called “back-calculation,” which Bacchetti and other researchers had already employed successfully to estimate the course of the HIV/AIDS epidemic. This technique calculates backward from current case numbers to recreate the original conditions that gave rise to the epidemic. It focuses on a much smaller number of assumptions, including guesses about how many people were infected by BSE, when they were infected, and the length of the incubation period. In all, the team used only seven variable parameters.

No matter how those seven parameters are varied, the upper limit of cases is “less than 10,000,” says London School statistical epidemiologist Simon Cousens, a co-author of the paper. For example, even if many millions of people have been infected with BSE, the small number of cases to date suggests that the average incubation time is so long that “most of those people will die of other causes before they develop clinical disease,” Cousens says. Conversely, if only a small number of people have been infected, the current case toll indicates that the average incubation time is fairly short.

Current vCJD case trends may lend some support to that conclusion, says Bacchetti. Although cases have been increasing about 20% to 25% annually over the past several years, the overall numbers are still quite small. Bacchetti says that the London School team's optimistic projections are “reasonable,” because “we now have many years with no sign of … explosive growth.”

But the Anderson team believes that the London School's figures paint too rosy a picture. Ferguson suspects that the group's lower numbers are due to “the methodological approximations employed and differences in key assumptions.” The most important reason for the difference, he says, is that the London School relied too heavily on reported cases of BSE in cattle before 1988, when health officials made reporting mandatory: “There is likely to have been really substantial underreporting of BSE cases in the early stages of the epidemic.” Cousens counters that even if much higher BSE rates were assumed, it would not change his group's overall results: The London School's projections came out lower even when it was assumed that up to 12,000,000 members of the British public had been infected by BSE-laden cattle.

Both models may be too optimistic, the two teams agree, if one of the key assumptions they both made turns out to be wrong: that all victims of vCJD will share the same genetic profile. One thing that most vCJD researchers do agree on is that wayward proteins called prions, aberrant versions of the normal cellular protein PrP, are responsible in whole or in part for vCJD, BSE, and a host of other neurodegenerative diseases in humans and animals. So far, all the people diagnosed with vCJD have shared one characteristic: Their PrP genes, which come in two copies, code for two copies of the amino acid methionine at position 129 in the corresponding PrP protein. These methionine homozygotes, as they are called, exist in 40% of the British population. But several studies of another human prion disease, kuru, have shown that although methionine homozygotes have shorter incubation times, other genotypes are also susceptible. If the entire British public were susceptible, rather than just 40%, note the London School researchers, their worst-case estimates might have to be multiplied by a factor of 2.5.

Another factor that could boost worst-case numbers, some scientists say, is if other genetic factors—including those unrelated to the PrP gene itself—also affect long-term susceptibility. Such uncertainties “undermine these kinds of predictions,” says neurologist John Collinge of St. Mary's Hospital in London, a longtime critic of attempts to mathematically model the epidemic.

Nevertheless, the London School researchers believe that if the fairly modest rise in new vCJD cases over the past few years does not dramatically increase, time may be on the side of their more optimistic projections. And because their study predicts that vCJD cases might reach a peak in the next few years, its accuracy should soon be clear. Says Woolhouse: “We will soon know if they are right.”

INFECTIOUS DISEASES

Is BSE in Sheep a No-Brainer?

Michael Balter

Efforts to mathematically model the epidemic of variant Creutzfeldt-Jakob disease (vCJD) in the United Kingdom are fraught with unknowns (see main text). But all bets would be off if it turned out that humans got the disease not only from mad cows but also from mad sheep. This possibility, which has given health officials nightmares in recent years, could eventually help fuel an explosion of vCJD cases (Science, 17 March 2000, p. 1906).

Last week, officials thought this bad news was about to break. An Edinburgh-based team from the U.K.'s Institute for Animal Health (IAH) was on the verge of publishing, in the online edition of the Journal of General Virology, experiments indicating that samples of sheep brain might be harboring bovine spongiform encephalopathy (BSE), or “mad cow disease.” But the paper was pulled at the last minute when the institute, doing a last check on the source of the samples, was told by an independent laboratory that the material it thought was sheep brain actually came from cattle. The IAH is now conducting an internal audit to see if this is indeed the case, and if so, how it could have made such a mistake.

Mad or not?

A lab mix-up leaves uncertain whether sheep harbor BSE.

CREDIT: M. BAYLIS

The episode has left the public reputation of the IAH—which has made some of the most important discoveries in this field—in tatters. “BSE Tests Conducted on Wrong Brains,” cried a headline in the London Times. But epidemiologist Peter Smith, chair of the government's Spongiform Encephalopathy Advisory Committee, says it “would be wise to withhold judgment” about what really happened. Smith adds that the affair provides “no reassurance” that sheep don't harbor BSE. Chris Bostock, IAH's chief, says that early this year the government's Veterinary Laboratories Agency (VLA)—which had previously done its own analysis of the samples—had reassured him that they appeared to be 100% sheep. But when a second lab concluded last week that it was all cattle brain, the team decided to withdraw the paper. Shortly afterward, Bostock says, the VLA contacted him to say its laboratory had analyzed the wrong samples and was now withdrawing its original reassurance that they were pure sheep.

Bostock complains that the British press has pronounced the IAH guilty of making a mistake before all the proof is in. “If there is an error on our part, we will state that,” he says. Until then, Bostock insists, there should be no rush to judgment: “We have to balance this with a decade of high-quality work in this field.”

Seeds of Discontent

Daniel Charles is the author of Lords of the Harvest: Biotech, Big Money, and the Future of Food, published this month.

Plant breeders, developing nations, and agricultural firms battle for control of the world's stock of crop diversity

For the past 10 years, at a research compound outside Harare, Zimbabwe, Marianne Bänziger has been painstakingly constructing corn plants that will thrive in drought-prone areas of southern Africa. Bänziger, a breeder for the International Center for the Improvement of Maize and Wheat (CIMMYT), collects pollen from the tassels of one plant, sprinkles it over the silk of another, and waits for another growing season to examine the results.

Earlier this year, CIMMYT announced that Bänziger's decade of labor had paid off: She had created several new lines of corn, or maize, dubbed “Grace” and “Zm521,” that exhibit remarkable vigor even when afflicted by drought. In field trials conducted in South Africa, these varieties produced 30% to 50% more corn than traditional varieties grown by small farmers in the area. In the depleted soils of Zimbabwe's communal lands, the new varieties performed as well as the best commercial hybrids. CIMMYT, a publicly funded research institute with headquarters outside Mexico City, will now make Grace and Zm521 seeds available free of charge to seed distributors around the world—one more tool in the giant task of growing crops to feed the world.

But Grace and Zm521 are products of a system under threat. To create the new strains, Bänziger drew on thousands of native varieties of corn from CIMMYT's extensive seed banks, which were built up through decades of free exchange with other seed banks around the globe. In recent years, however, many nations have invoked a 1993 international treaty on biodiversity to block access to their seed collections and prohibit export of “genetic resources,” fearing that they might be giving away valuable property. As a result, CIMMYT and other international seed banks have found it increasingly difficult to add to their collections.

This breakdown of seed exchanges threatens the lifeblood of plant breeding, according to some observers—including some of the prime movers behind the 1993 biodiversity treaty. They fear that if breeders don't have free access to the planet's genetic diversity, they will be increasingly hampered in their efforts to develop crops that resist disease and pests, or that thrive under shifting climate. This is particularly worrisome for breeders in the developing world, such as Bänziger, who rely on seed collections that are most directly threatened by moves to nationalize genetic resources.

To head off that threat, a new international treaty, drafted but not yet signed, attempts to revive international seed exchanges with financial incentives. Under the draft agreement, commercial seed companies that use samples from public seed banks to breed new privately owned varieties will have to pay royalties to a fund to be established under the auspices of the United Nations' Food and Agriculture Organization (FAO). The proceeds would then go into a common fund to be distributed among member countries, probably to support seed banks and conservation projects. Nonprofit outfits like CIMMYT, which distribute varieties free of charge, would be exempt from paying royalties.

Some important disputes remain to be resolved, but the treaty—formally known as the revised International Undertaking on Plant Genetic Resources—is scheduled for signing at a high-level meeting at the FAO set for 2 to 13 November in Rome.

African corn.

Marianne Bänziger with her hardy corn plants in Zimbabwe.

CREDIT: CIMMYT

Surprisingly, seed companies and the biotechnology industry appear to be taking the proposed treaty in stride, while scientists in charge of gene banks are distinctly unenthused. Seed companies are accustomed to paying for the use of genes or plant varieties, notes Stephen Smith, a research fellow at Pioneer Hi-Bred International in Des Moines, Iowa. Perhaps, he says, the prospect of future profits may even induce gene banks to uncover hidden treasures within their own collections. For the seed banks, however, the system could be a logistical headache. “We're having trouble imagining, from a practical point of view, how this [tracking seed use] would work,” says Peter Bretting, a manager of gene banks operated by the U.S. Department of Agriculture (USDA). And there is also “a sense of sadness” among gene bank administrators, says one government official. “For 4 decades now, the U.S. has stood by a philosophy of open access. And they are seeing that system [being] shut down or changed.”

Smashing rocks together

The genealogy of Bänziger's maize varieties shows how free exchanges work. The ancestors of Grace and Zm521 were “landraces,” or traditional varieties of corn grown by farmers in the Latin American countryside. Some landraces had originally been collected by CIMMYT, some by Latin American research institutes, and some by U.S. researchers who deposited their collections in U.S. seed banks. Some seeds then found their way from the United States to Kenya and Egypt before they arrived at CIMMYT. Before Bänziger ever started her work, CIMMYT's breeders had subjected the landraces to repeated cycles of inbreeding and selection. By thus concentrating particular genes within a population, breeders uncovered previously hidden genetic traits, in this case an ability to withstand drought. “The original landraces do not show the trait,” Bänziger says.

Bänziger selected 50 breeding lines from among several thousand in CIMMYT's collection and set to work crossing the various lines in her test plots, shuffling and reshuffling the genetic combinations represented by each line of corn. The process, she says, “is like collecting big stones from all over the world. You smash them together to make small stones, and with that you make a mosaic.” Ten years later, she had Grace and Zm521.

Golden kernels.

Corn seeds like these in CIMMYT's seed bank are valuable to plant breeders.

CREDIT: A. M. SANCHEZ/CIMMYT

Similar stories can be told about the origins of any new variety of a major crop, whether created by research stations in Asia or profit-driven seed companies in Des Moines or St. Louis, and whether created solely by traditional breeding or in part by molecular genetic engineering. Every variant form of wheat, maize, or potato traces its lineage back to the genetic diversity found in an ancestral homeland. Soybeans came from China, potatoes from Latin America, sorghum from Africa, and so on.

North vs. South

In the 1990s, the system of free exchange began to unravel. Ironically, the roots of its downfall lie in a campaign begun by people who wanted to preserve it. Agricultural activists saw a threat to free exchange from private control over seeds and, specifically, from laws that allow companies to claim intellectual property rights over new plant varieties or the genes that they contain. These activists fought what they saw as exploitation of cash-poor but gene-rich developing nations by gene-hungry multinational corporations. Among the most prominent of the campaigners were Cary Fowler, Pat Mooney, and Hope Shand, co-founders of the Rural Advancement Foundation International (RAFI), a nonprofit based in Canada. “We were talking about these resources being the common heritage of humankind, our common responsibility,” says Fowler.

Over the years, many Third World governments became persuaded that their fields and forests harbor genetic treasures, and many decided to claim those treasures for themselves. The international Convention on Biological Diversity, which entered into force in 1993, provided the legal framework: It declared that genetic resources—every rock and pebble in Bänziger's mosaic—were subject to the control of the nations on whose territory these resources were found. More than 50 nations have since enacted laws restricting the export of plants, seeds, and other biological materials from their forests or gene banks. First World seed banks have found it nearly impossible to collect additional plants or seeds from many foreign fields (see graph), according to USDA officials. Although some companies may be able to buy access to valuable collections, such restrictions could place useful seeds beyond the reach of nonprofit breeders such as Bänziger.

Free trade?

USDA officials seeking seed samples from other nations have begun to get rebuffed.

SOURCE: USDA

This turn of events has placed the original critics of “biopiracy” in an awkward position. After spending most of his life railing against the evils of multinational corporations, Mooney of RAFI (which recently changed its name to the ETC Group) now finds himself condemning the legal walls that Third World governments are building around seed banks. “Forcing farmers and other researchers to reduce their options and [restrict] their access to diversity is irresponsible. It is the flip side of intellectual property monopoly and equally immoral,” he wrote earlier this year.

Furthermore, those restrictions on seed transfers are likely to hurt developing countries most, notes Fowler, who left RAFI nearly a decade ago and now works as an adviser to the International Plant Genetic Resources Institute (IPGRI) in Fiumicino, Italy. In collaboration with two other researchers at IPGRI, Fowler recently published data showing that agriculture in nearly all developing nations relies on crops that originated somewhere else. Africans, for instance, depend heavily on maize and cassava, both imported from abroad. New varieties of these crops will depend on genetic resources found originally in Latin America and Asia.

Moreover, says Fowler, genetic resources now flow mainly from “North” to “South” rather than the other way around. In one recent typical year, for every single seed sample that developing nations sent to international gene banks, those gene banks sent about 60 samples back. Farmers in poor nations now depend on seeds held by gene banks located in or funded by rich nations. For Fowler, the conclusion is obvious: If poor nations create a world in which they have to bargain for access to the genetic resources in these banks, they lose.

Out of the pot

In effect, such bargaining began during negotiations leading to the proposed treaty. The treaty attempts to break the logjam over seeds by creating a way for Third World nations to profit from the riches stored in the world's public seed banks, including the national seed banks of the United States and various European nations. It establishes a common pot of seeds that will be freely available to plant breeders, in exchange for royalties if the seeds are used to develop commercial varieties. For example, if a commercial seed company used seeds from Grace and Zm521 to breed new proprietary varieties, it then would have to pay royalties into the common fund. (Pharmaceutical and other nonfood uses are excluded.) This common pot, called the “multilateral system,” currently contains seeds from about 30 of the world's major crops, including corn, wheat, rice, potatoes, bananas, and beans. All seeds from these crops in all the public databases of signatory countries would be included.

Soybeans, however, are not in that common pot, because China, the homeland of soybeans, objected to its inclusion. Latin American nations, meanwhile, refused to include tomatoes or groundnuts such as peanuts, and African nations kept a variety of tropical grasses off the list. In order to obtain samples of these crops from national gene banks, researchers will have to obtain special permission and perhaps buy access. Some predict that this will severely hamper efforts to develop better varieties of such crops, many of which get little attention from breeders anyway. “The implication is, they really think that they can make money by selling these genetic resources,” says one European observer in apparent disbelief.

Seeking agreement.

Ethiopia's Egziabher and Fowler, representing international researchers, testified in Rome.

CREDIT: A. HENRY/IISD

In reality, however, a Third World gene cartel isn't likely to squeeze much money from the agricultural seed industry. Unlike the pharmaceutical industry, seed companies generate relatively meager profits—less than half a billion dollars each year worldwide. In the case of some plants for which Third World nations might control unique genetic resources, such as tropical grasses, a commercial seed industry doesn't even exist.

During plenary sessions of the negotiations, excerpts of which were published on the Internet,* delegates spoke in high-minded tones about the need to include as many crops as possible in the multilateral system, in order to assure food security for the world's poor. In private, many delegates refused to give up control over genetic resources that they considered valuable. Two participants in one small negotiating session on the final day describe the following episode: Latin American delegates turned to their Asian colleagues and offered to include tomatoes, peanuts, and a few other crops in the common pot if Asia agreed to include soybeans, sugarcane, and oil palm. Asia's representatives refused. The Latin Americans then turned to Africa's representatives and offered to include their tropical legumes in exchange for the Africans' tropical grasses. The Africans declined.

Progress on the list of crops, suggested Tewolde Berhan Gebre Egziabher of Ethiopia, one of the leading spokespersons for the developing nations, may depend on resolution of another sticky issue: the patenting of plant genes. African nations, in particular, have demanded a ban on the patenting of anything discovered within public seed banks. The United States, supported by Australia and Canada, agreed that patents shouldn't be allowed on plant varieties obtained from public gene banks; such varieties, they argued, wouldn't be patentable anyway under U.S. law. The United States and its allies adamantly refused, however, to ban patents on “genetic parts and components,” referring to individual genes that might be isolated from the seeds and transferred to other species via genetic engineering.

This dispute will be taken up again in November, at the meeting where the treaty is supposed to be signed. “If they can fix 15 words, it'll happen,” says one industry observer. It's also possible that most nations will go forward with the treaty, even without agreement from the United States.

Tangled tree.

To create a single rice variety, breeders drew on many strains from around the world.

If the treaty is signed, USDA's Bretting foresees big problems in implementing it. He says he has no idea how USDA's gene banks could track the use of their seeds in commercial products in order to collect royalties. When a particular sample of seeds leaves a public gene bank, it “goes into the gene pool and is crossed with a gazillion different things.” Twenty years later, it could become one distant ancestor of a commercial product. “Who's going to track this?” Bretting asks.

Meanwhile, the thorny questions of how much the commercial seed companies will pay—and exactly how the common monies will be administered and distributed to member countries—have been left to the treaty's “governing body,” which is yet to be created. During the negotiations, a group of African nations suggested that public gene banks might generate annual royalties of half a billion dollars or more. Industry representatives roll their eyes at such numbers and point out that this sum would exceed the current global profits of the commercial seed industry. A more realistic estimate of potential revenues, they say, might be a few million dollars, beginning a decade or more down the road. “The belief that there's gold in those hills just waiting to be extracted is really unfortunate,” says Jeffrey Kushan, a lawyer with the Washington, D.C., office of Powell, Goldstein, Frazer & Murphy, which represents the U.S. Biotechnology Industry Organization. Because the governing body is supposed to operate by consensus, such differences could lead to paralysis, leaving all seed exchanges in legal limbo.

On one point, however, there seems to be unanimity: There's no going back to the informal practices of an earlier era. Whether justified by the Convention on Biological Diversity, national laws, or the new treaty, government controls over seed exchanges are now a fact of life. “The era of free exchange,” says Stephen Smith of Pioneer Hi-Bred, “is gone.”

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